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PubMed2006

Genetics of body condition score in New Zealand dairy cows.

Body condition score (BCS) data were collected on 169,661 first-parity cows from herds participating in progeny testing schemes and linear type assessment. Genetic and residual variances for BCS estimated across time using a quadratic random regression model were found to be largest at the start of lactation. Heritability estimates ranged from 0.32 to 0.23 from d 1 to 200 of lactation, with a mean of 0.26. Genetic correlations between BCS and other traits were estimated using 2 approaches: 1) a multivariate analysis that included BCS and live weight, both adjusted for stage of lactation; 270-d cumulative yields of milk, fat, and protein; average somatic cell score; and 2 measures of fertility; and 2) a bivariate random regression analysis in which BCS was considered to be a longitudinal trait across time, with the same measurements as in approach 1 for all other traits. Genetic correlations of BCS with the 2 fertility traits were 0.43 and 0.50 using the multivariate analysis; the corresponding random regression estimates between BCS as a longitudinal trait across time and 2 measures of fertility were 0.35 to 0.44 and 0.40 to 0.49, and tended to increase with stage of lactation. Genetic correlations estimated using the random regression model fluctuated around the multivariate estimates for live weight and somatic cell score, which were 0.50 and -0.12, respectively. Genetic correlations estimated using the multivariate analysis of BCS with fat and protein yields were close to zero. With the random regression model, genetic correlations between BCS and fat and protein yields were positive at d 1 of lactation (0.16 and 0.08, respectively) and were negative by d 200 of lactation (-0.25 and -0.20, respectively). In pastoral production systems, such as those typical in New Zealand, there appears to be an advantage in the total lactation yields of fat and protein for cows of higher BCS in early lactation, which is likely to be because these cows have body reserves that are available to be mobilized in later lactation, when feed resources are sometimes limited.

Animals↗

PubMed1999

Estimation of heritabilities and correlations associated with milk color traits.

The objective of this study was to estimate the genetic parameters associated with milk color traits of dairy cattle. The data consisted of test day records of 9516 first lactation dairy cows and the records of 6358 of these cows that went on to produce a second lactation. Friesians, Jerseys, and crossbred cows were included in the data. Test day records included measures of milk, fat, and protein as well as milk color measured as absorbance at 450 nm. From these measurements, fat color and beta-carotene yield were calculated. Analyses were performed both within and across breeds. Jerseys produced more beta-carotene than did Friesians, and milk and fat from Jerseys had more intense color. Lactation model estimates for the heritabilities of milk color traits ranged from 0.33 to 0.44 (across breed), 0.40 to 0.49 (Friesians), and 0.17 to 0.31 (Jerseys). In all analyses, the heritability estimates associated with beta-carotene yield were lower than the estimates associated with the color of milk or fat. Genetic correlations between beta-carotene yield and the production traits were positive, but genetic correlations between fat color and production traits were generally negative. Genetic correlations between milk color and milk and protein yields were negative, and the correlations with fat yield were close to zero.

Animals↗

PubMed2003

B19 virus genome diversity: epidemiological and clinical correlations.

Genetic analysis of parvovirus B19 has been carried out mainly to establish a framework to track molecular epidemiology of the virus and to correlate sequence variability with different pathological and clinical manifestations of the virus. A good amount of information regarding B19 virus sequence variability is available, and presently there are about 400 sequence records deposited in the nucleotide database of NCBI. A few are almost complete genomic sequences, and these allow the construction of a global alignment framework. Many others are partial genomic sequences, limited to selected regions, and these allow comparison of a higher number of isolates from well-defined epidemiological settings and/or pathological conditions. Most studies showed that the genetic variability of B19 virus is low, that molecular epidemiology is possible only on a limited geographical and temporal setting, and that no clear correlations are present between genome sequence and distinctive pathological and clinical manifestations. More recently, several viral isolates have been identified that show remarkable sequence diversity with respect to reference sequences. The identification of variant isolates added to the knowledge of genetic diversity in this virus group and allowed the identification of three divergent genetic clusters, about 10% divergent from each other and still quite distinct from other parvoviruses, that can be thought of as different genotypes within the human erythrovirus group and that show clearly resolved phylogenetic relationship. These variant isolates pose interesting questions regarding the real extent of genetic variability in the human erythroviruses, the relevance of these viruses in terms of epidemiology and their possible implication in the pathogenesis of erythrovirus-related diseases.

Genes, Viral↗

PubMed1982

Genetic parameters for testes size and sperm number in Hereford bulls.

Paternal half-sib heritability and genetic correlation estimates were obtained utilizing data from 578 Hereford bulls from 66 sires. Bulls were maintained in three lines (weaning weight, postweaning gain and control) of an ongoing selection project. Growth performance traits studied were adjusted 205-d weaning weight, 365-d weight, individual feed efficiency, sonoray fat thickness and postweaning gain. Heritability estimates for these traits were .15 +/- .17, .33 +/- .19, .46 +/- .21, .28 +/- .18 and .52 +/- .21, respectively. Scrotal measurements taken were circumference of both testes and length and diameter of right testis at 205 and 365 d of age. Heritability estimates were .08 +/- .20, .07 +/- .20 and .28 +/- .24 at 205 d, and .44 +/- .24, .16 +/- .21 and .40 +/- .24 at 365 d, respectively. Excised testes traits, circumference, right testis length, diameter and weight, total sperm in the testes and sperm/gram of testes had heritability estimates of .21 +/- .26, .19 +/- .26, .02 +/- .24, .63 +/- .27, .14 +/- .21 and -.13 +/- .18, respectively. Genetic correlations of scrotal measurements at 205 d with scrotal measurements at 365 d and excised testes traits were negative. Scrotal measurements at 365 d had high positive genetic correlations with excised testes size, weight and total sperm. These relationships suggest that selection for increase of scrotal size at 365 d should increase testes size and weight and sperm numbers. Genetic correlations of weights and gain with scrotal measurements at 365 d and excised testes characteristics were moderate to high, in a favorable direction. Genetic correlations of testes traits with feed efficiency were essentially zero, while those with fat thickness were moderately positive. These results suggest that increasing testes size should not adversely affect growth performance traits except through the reduction in selection intensity.

Animals↗

PubMed1989

[Correlation of genetic and demographic differences between populations of indigenous inhabitants of the Northeastern USSR].

Correlative analysis is given for some demographic characteristics in populations of asiatic eskimos, coastal and reindeer chuckchies, Kamchatka koryaks and Chukotka evens. Summarized estimation of population differences for 7 demographic parameters is presented. Highly reliable correlation of genetic distinctions as defined for 17 polymorphic loci, and demographic differences between populations estimated for 7 parameters (r = 0.868, P less than 0.001) was found. The role of ecological factors in formation of genetic structure features and application of demographic characteristics, as possible indicator of ecological particularities of the given populations, is considered.

Demography↗

PubMed2004

Genetic relationships between calving and carcass traits for Charolais and Hereford cattle in Sweden.

The objective of this study was to estimate genetic correlations between calving difficulty score and carcass traits in Charolais and Hereford cattle, treating first and later parity calvings as different traits. Genetic correlations between birth weight and carcass traits were also estimated. Field data on 59,182 Charolais and 27,051 Hereford calvings, and carcass traits of 5,260 Charolais and 1,232 Hereford bulls, were used in bivariate linear animal model analyses. Estimated heritabilities were moderate to high (0.22 to 0.50) for direct effects on birth weight, carcass weight, and (S)EUROP (European Community scale for carcass classification) grades for carcass fleshiness and fatness. Heritabilities of 0.07 to 0.18 were estimated for maternal effect on birth weight, and for direct and maternal effects on calving difficulty score at first parity. Lower heritabilities (0.01 to 0.05) were estimated for calving difficulty score at later parities. Carcass weight was positively genetically correlated (0.11 to 0.53) with both direct and maternal effects on birth weight and with direct effects on calving difficulty score. Carcass weight was, however, weakly or negatively (-0.70 to 0.07) correlated with maternal calving difficulty score. Higher carcass fatness grade was genetically associated with lower birth weight, and in most cases, also with less difficult calving. Genetic correlations with carcass fleshiness grade were highly variable. Moderately unfavorable correlations between carcass fleshiness grade and maternal calving difficulty score at first parity were estimated for both Charolais (0.42) and Hereford (0.54). This study found certain antagonistic genetic relationships between calving performance and carcass traits for both Charolais and Hereford cattle. Both direct and maternal calving performance, as well as carcass traits, should be included in the breeding goal and selected for in beef breeds.

Animals↗

PubMed2004

Body condition scores and dairy form evaluations as indicators of days open in US Holsteins.

The objectives of this study were to estimate genetic correlations among body condition score (BCS), dairy form, milk yield, and days open in US Holsteins and investigate the potential of using BCS or dairy form evaluations as early indicators of days open. Dairy form and BCS obtained from the Holstein Association USA, Inc., were merged with mature equivalents (ME) for milk yields and days open data from AIPL-USDA. Cows were required to be classified between 24 and 60 mo of age, before 335 d in milk (DIM) and have ME milk of at least 4537 kg. A minimum of 20 daughters per sire and 10 cows per herd-classification visit (HV) or herd-year-season of calving (HYS) were required. The final data set included 159,700 records. Heritabilities and correlations among dairy form, BCS, milk yield, and days open were estimated with multiple trait sire models. Fixed effects included age at classification for dairy form and BCS, age at calving for milk yield, HV for dairy form and BCS, HYS for milk yield and days open, DIM within lactation group for dairy form and BCS and lactation group for milk yield and days open. Correlations among dairy form, BCS, and days open were generated with and without a ME milk covariable. Correlations between ME milk and days open were generated with and without covariables for dairy form or BCS. Random effects included sire and error. The genetic correlation estimates of days open with dairy form, BCS, and ME milk were 0.48, -0.30, and 0.38, respectively. The genetic correlation estimate between days open and dairy form was 0.38 after adjustment for ME milk, whereas the genetic correlation between days open and BCS was -0.24 after adjustment for ME milk. Combining dairy form evaluations with days open evaluations for 19 recently proven bulls resulted in an average increase of 0.06 for reliability of days open evaluations. The addition of BCS evaluations did not increase reliability when dairy form observations were available.

Aging↗

PubMed2026

Shared genetic architecture of obesity and gastroesophageal reflux disease.

Obesity is identified as a risk factor of gastroesophageal reflux disease (GERD). This study aims to elucidate the shared genetic architecture of obesity-related phenotypes and GERD. Based on the publicly available genome-wide association studies' datasets, this genome-wide pleiotropic association study was conducted with various genetic approaches (including linkage disequilibrium score regression, high-definition likelihood inference for genetic correlations, pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation, Bayesian colocalization, summary-based Mendelian randomization, and multi-marker analysis of genomic annotation analysis) sequentially to unravel the genetic associations from single-nucleotide polymorphism to gene levels, and to reveal the underlying shared genetic architecture between obesity-related phenotypes and GERD. This study discovered shared genetic mechanisms between GERD and several obesity-related phenotypes, including arm fat percentage (left), arm fat percentage (right), leg fat percentage (left), leg fat percentage (right), trunk fat percentage, waist-to-hip ratio, and body mass index. Significant genetic correlations were observed by linkage disequilibrium score regression and high-definition likelihood inference for genetic correlations, with multiple associated pleiotropic loci and their mapped genes identified by pleiotropic analysis under composite null hypothesis, Functional Mapping and Annotation, Bayesian colocalization, summary-based Mendelian randomization, and multi-marker analysis of genomic annotation analysis. Additionally, several brain tissues were identified to be linked to both obesity and GERD by multi-marker analysis of genomic annotation. This research provided strong evidence of genetic correlations and brought novel insights into the underlying genetic connections and shared genetic architectures of obesity and GERD.

Humans↗

PubMed1991

The evolution of social communication systems in a subdivided population.

Evolution of social communication systems is modeled with a quantitative genetic model. The mathematical model describes the coevolutionary process of a social signal (a social character) and responsiveness (a social preference) to the signal. The responsiveness is postulated to influence fitness of senders of the signal. Considerations are extended to subdivided population structure by combining the social selection model with a group selection model. The numerical results derived from the models indicate that the evolutionary rate of social communication systems depends largely on genetic correlation between the signal and the responsiveness. Group selection can reinforce the evolutionary rate and relax its dependence on genetic correlation. The origin of genetic correlation is discussed in relation to group selection.

Animal Communication↗

PubMed2005

Threshold-linear estimation of genetic parameters for farrowing mortality, litter size, and test performance of Large White sows.

Up to 109,447 records of 49,656 Large White sows were used to evaluate the genetic relationship between number of pigs born dead (BD) and number born alive (BA) in first and later parities. Performance data (n = 30,832) for ultrasound backfat (BF) at the end of the test and days to reach 113.5 kg (AD) were used to estimate their relationships with BD and BA at first parity in a four-trait threshold-linear analysis (TL). Effects were year-farm, contemporary group (CG: farm-farrowing year-farrowing month) and animal additive genetic. At first parity, estimates of heritability were 0.09, 0.09, 0.37, and 0.31 for BA, BD, AD, and BF, respectively. The estimate of genetic correlation between BD and litter size was -0.04 (BD-BA). Corresponding values with test traits were both -0.14 (BD-AD, BD-BF). Estimates of genetic correlation between BA and performance traits were 0.08 (BA-AD) and 0.05 (BA-BF). The two test traits were moderately negatively correlated (-0.22). For later parities, a six-trait (BD, BA in three parities) TL model was implemented. The estimates of additive genetic variances and heritability increased with parity for BD and BA. Estimates of heritabilities were: 0.09, 0.10, and 0.11 for BD, and 0.09, 0.12, and 0.12 for BA in parities one to three, respectively. Estimates of genetic correlations between different parities were high (0.91 to 0.96) for BD, and slightly lower (0.74 to 0.95) for BA. Genetic correlations between BD and BA were low and positive (0.02 to 0.17) for BA in Parities 1 and 2, but negative (-0.04 to -0.10) for BA in Parity 3. Selection for increased litter size should have little effect on farrowing piglet mortality. Intense selection for faster growth and increased leanness should increase farrowing piglet mortality of first-parity sows. A repeatability model with a simple correction for the heterogeneity of variances over parities could be implemented to select against farrowing mortality. The genetic components of perinatal piglet mortality are independent of the ones for litter size in the first parity, and they show an undesirable, but not strong, genetic association in second parity.

Animals↗

PubMed1993

Estimates of variances due to direct and maternal effects for growth traits of Romanov sheep.

Records of growth traits of 2,086 Romanov lambs were used to estimate variance components for an animal model and genetic correlations between growth traits. Traits analyzed were birth weight (BWT), weaning weight (WW), 90-d weight (W90), and daily gain for the periods birth to weaning (DG1) and weaning to 90 d (DG2). Weaning was at approximately 40 d. Variance components were estimated using restricted maximum likelihood with an animal model including fixed effects for year x season, sex, rearing type, and litter size and random effects for the direct genetic effect of the animal (with relative variance h2), the maternal genetic effect (with relative variance m2), the permanent environmental effect (with relative variance c2), and random residual effect. Genetic correlations were estimated for a model with the same fixed effects and only additive genetic effects. Estimates of the variances of random effects, h2, m2, and c2, respectively, as a proportion of phenotypic variance were .04, .22, .10 (BWT); .34, .25, .0 (WW); .09, .01, .07 (W90); .26, .17, .02 (DG1); and .15, .01, .03 (DG2). Estimates of genetic correlations were .12 (BWT with WW); .24 (BWT with W90); .48 (WW with W90); .69 (DG1 with DG2); -.01 (BWT with DG1); .05 (BWT with DG2); .59 (WW with DG1); .47 (WW with DG2); .67 (W90 with DG1); and .98 (W90 with DG2). Results suggest that selection should be effective for WW, DG1, and DG2 but less effective for BWT and W90. An important maternal effect was observed for BWT, WW, and DG1. The estimates of genetic correlations showed no genetic antagonisms among the traits.

Analysis of Variance↗

PubMed2006

Variance components analyses of multiple asthma traits in a large sample of Australian families ascertained through a twin proband.

BACKGROUND: Intermediate phenotypes are often measured as a proxy for asthma. It is largely unclear to what extent the same set of environmental or genetic factors regulate these traits. OBJECTIVE: Estimate the environmental and genetic correlations between self-reported and clinical asthma traits. METHODS: A total of 3,073 subjects from 802 families were ascertained through a twin proband. Traits measured included self-reported asthma, airway histamine responsiveness (AHR), skin prick response to common allergens including house dust mite (Dermatophagoides pteronyssinus [D. pter]), baseline lung function, total serum immunoglobulin E (IgE) and eosinophilia. Bivariate and multivariate analyses of eight traits were performed with adjustment for ascertainment and significant covariates. RESULTS: Overall 2,716 participants completed an asthma questionnaire and 2,087 were clinically tested, including 1,289 self-reported asthmatics (92% previously diagnosed by a doctor). Asthma, AHR, markers of allergic sensitization and eosinophilia had significant environmental correlations with each other (range: 0.23-0.89). Baseline forced expiratory volume in 1 s (FEV(1)) showed low environmental correlations with most traits. Fewer genetic correlations were significantly different from zero. Phenotypes with greatest genetic similarity were asthma and atopy (0.46), IgE and eosinophilia (0.44), AHR and D. pter (0.43) and AHR and airway obstruction (-0.43). Traits with greatest genetic dissimilarity were FEV(1) and atopy (0.05), airway obstruction and IgE (0.07) and FEV(1) and D. pter (0.11). CONCLUSION: These results suggest that the same set of environmental factors regulates the variation of many asthma traits. In addition, although most traits are regulated to great extent by specific genetic factors, there is still some degree of genetic overlap that could be exploited by multivariate linkage approaches.

Asthma↗

PubMed1989

Genetic analysis of fertility traits in Israeli dairy cattle.

First through third parity lactation records of 91,770 Israeli Holsteins inseminated between 1980 and 1986 were evaluated by univariate mixed model methodology for fertility and production traits. The analytical model included the effects of herd-year-season, group of sires, sire, cow, and residual. Sire, cow, and residual were random: all other effects were fixed. Sires were assumed to be unrelated. Variance components were computed separately for first and second parity by Henderson's method 3. First parity heritabilities were .035 for conception status [1/number of inseminations to conception], .048 for days from calving to first breeding, and .135 for milk production. Corresponding second parity heritabilities were .022, .031, and .125. First parity genetic correlations were -.02 between conception status and milk, .27 between days to first breeding and milk, and -.03 between the two fertility traits. All environmental correlations, and all second parity genetic correlations among these traits, were between -.2 and .2. Genetic trends, estimated as twice the regression of the evaluation of the cow's sire on calving date, were 1% for conception status, .1 for days to first breeding, and 154 kg milk/yr. Thus, there was no indication of an adverse genetic relationship between fertility and milk production in this population.

Animals↗

PubMed2006

Genetic parameters for functional traits in dairy cattle from daily random regression models.

The objective of the research was to estimate genetic parameters, such as heritabilities and genetic correlations, using daily test day data for milk yield (MY), milking speed (MS), dry matter intake (DMI), and body weight (BW) using random regression methodology. Data were from first lactation dairy cows (n = 320) from the Chamau research farm of the Swiss Federal Institute of Technology, Switzerland over the period from April 1994 to 2004. All traits were recorded daily using automated machines. Estimated heritabilities (h(2)) varied from 0.18 to 0.30 (mean h(2) = 0.24) for MY, 0.003 to 0.098 (mean h(2) = 0.03) for MS, 0.22 to 0.53 (mean h(2) = 0.43) for BW, and 0.12 to 0.34 (mean h(2) = 0.23) for DMI. A permanent environmental effect was included in both the univariate and bivariate models, but was assumed constant in estimating some genetic correlations because of convergence problems. Estimated genetic correlations varied from 0.31 to 0.41 between MY and MS, from -0.47 to 0.29 between MY and DMI, from -0.60 to 0.54 between MY and BW, from 0.17 to 0.26 between MS and DMI, from -0.18 to 0.25 between MS and BW, and from -0.89 to 0.29 between DMI and BW. Genetic correlations for MY, MS, DMI, and BW from calving to midlactation decreased similarly to 0.40, 0.36, 0.14, and 0.36 and, at the end of the lactation, decreased to -0.06, 0.23, -0.07, and 0.09, respectively. Daily genetic variance-covariance of many functional traits are reported for the first time and will be useful when constructing selection indexes for more than one trait based on longitudinal genetic parameters.

Animals↗

PubMed2003

Genetic parameters for body condition score, body weight, milk yield, and fertility estimated using random regression models.

Genetic (co)variances between body condition score (BCS), body weight (BW), milk yield, and fertility were estimated using a random regression animal model extended to multivariate analysis. The data analyzed included 81,313 BCS observations, 91,937 BW observations, and 100,458 milk test-day yields from 8725 multiparous Holstein-Friesian cows. A cubic random regression was sufficient to model the changing genetic variances for BCS, BW, and milk across different days in milk. The genetic correlations between BCS and fertility changed little over the lactation; genetic correlations between BCS and interval to first service and between BCS and pregnancy rate to first service varied from -0.47 to -0.31, and from 0.15 to 0.38, respectively. This suggests that maximum genetic gain in fertility from indirect selection on BCS should be based on measurements taken in midlactation when the genetic variance for BCS is largest. Selection for increased BW resulted in shorter intervals to first service, but more services and poorer pregnancy rates; genetic correlations between BW and pregnancy rate to first service varied from -0.52 to -0.45. Genetic selection for higher lactation milk yield alone through selection on increased milk yield in early lactation is likely to have a more deleterious effect on genetic merit for fertility than selection on higher milk yield in late lactation.

Animals↗

PubMed1991

Relationship of fertility to milk yield in Swedish cattle.

Data consisted of 48,830 and 21,136 records of Swedish Red and White and Swedish Black and White cattle. Fertility in virgin heifers and in first lactation cows was measured by first service pregnancy rate and number of services per pregnancy. Production trait considered was FCM produced in first 100 d of lactation. The heritabilities for fertility traits in virgin heifers and first lactation cows were about .05 in both breeds. The genetic correlations between fertility measures within parity were close to one in both breeds, suggesting that these were measures of the same trait. The genetic correlations between fertility in virgin heifer and in first lactation were about .88 for Swedish Red and White breed and between .6 and .7 for Swedish Black and White breed. The association between fertility and production in first lactation cows was antagonistic, with genetic correlations between first service pregnancy rate and milk yield of -.13 and -.32 for Swedish Red and White and Swedish Black and White breed, respectively. The association between first service pregnancy rate in virgin heifers and milk yield in first lactation was also antagonistic, with genetic correlations of -.14 and -.41 for Swedish Red and White and Swedish Black and White breed, respectively.

Animals↗

PubMed1993

Efficiency of an approximate animal model for maternal and direct genetic effects of litter size in swine.

A simulated population of 120 sows and 24 boars in service per year was used to compare genetic evaluations for first-parity litter size and selection response when approximate and complete animal models were used. The complete animal model included maternal and direct effects. The approximate model did not account for covariances between maternal breeding values, or between maternal and direct breeding values, but included a random litter effect of birth of sow. After 10 yr of selection, the overall response (maternal plus direct) was 2.94, 1.61, and .77 pigs using the approximate model and 3.11, 1.65, and .67 pigs using the complete model with equal weighting of maternal and direct genetic effects in the aggregated breeding value for genetic correlations between maternal and direct effects of 0, -.5, and -.9, respectively. Higher reduction was obtained in direct genetic response that was 5, 8, and 19% lower using the approximate model than the complete model for genetic correlations of 0, -.5, and -.9, respectively. Use of the approximate model over 10 yr of selection resulted in a bias of estimation of direct genetic trend of .24, .54, and .48 pigs and in bias in estimated overall response (maternal plus direct) of -.49, .67, and 1.28 pigs for genetic correlations between maternal and direct effects of 0, -.5, and -.9, respectively. Bias in environmental trend estimated from year-season effects was of the same magnitude as the bias in estimated overall response but with an opposite sign. With the approximate model, maternal genetic response was due to a correlation between maternal genetic effects and direct EBV, which for an embedded trait such as maternal genetic effects occurred even when there was no correlation between their true genetic effects. Findings suggested that over the short term the approximate model can be used without substantial loss of overall response but the use of the complete model was recommended because of unbiased estimates in genetic and environmental trend and higher direct genetic response.

Animals↗

PubMed2026

Multi-trait GWAS identifies pleiotropic loci shared between early pregnancy bleeding and psychiatric traits.

INTRODUCTION: Early pregnancy bleeding is a common pregnancy complication, yet its genetic basis and potential links with psychiatric traits remain poorly understood. This study aimed to characterize the shared genetic architecture between early pregnancy bleeding and reproductive, psychiatric, and cardiometabolic traits. METHODS: We integrated linkage disequilibrium score regression (LDSC), local genetic correlation analysis (LAVA), and multi-trait genome-wide association analysis (MTAG). LDSC was used to estimate genome-wide genetic correlations, including sex-stratified analyses. LAVA was applied to identify genomic regions contributing to local genetic sharing. Guided by these correlation patterns, MTAG was performed to improve locus discovery, followed by cis-eQTL analysis using GTEx v8 to explore potential regulatory mechanisms. RESULTS: LDSC revealed significant positive genetic correlations between early pregnancy bleeding and reproductive traits, including endometriosis, miscarriage, and uterine fibroids. Strong positive correlations were also observed with several psychiatric disorders, including major depressive disorder, post-traumatic stress disorder, and attention deficit hyperactivity disorder. Sex-stratified analyses suggested stronger genetic correlations with emotional reactivity-related traits in females, whereas social and behavioral traits were more prominent in males. LAVA localized these shared signals to specific genomic regions and identified pleiotropic hotspots at 8q21 near RUNX1T1 and 9p21 near CDKN2A/B. MTAG identified two novel loci, 15q15.1 marked by rs45457497 and 11q13.1 marked by rs2452681. Cis-eQTL analysis showed that the lead variant at 15q15.1 regulates RMDN3 expression across multiple brain regions, while the 11q13.1 locus regulates PACS1, GAL3ST3, and SF3B2 expression in brain tissues and the pituitary. DISCUSSION: These findings position early pregnancy bleeding as a multifactorial trait shaped by shared reproductive, psychiatric, neuroendocrine, and stress-related biology. The implication of RMDN3, which encodes a mitochondrial outer membrane protein involved in ER-mitochondria tethering and calcium homeostasis, suggests a potential molecular link between neuroendocrine stress pathways, psychiatric susceptibility, and reproductive vulnerability.

RMDN3↗